Research Overview—

Diabetic peripheral neuropathy (DPN) is a prevalent and severe complication of prolonged diabetes. As the probability of developing DPN increases with the duration of diabetes, the trend toward an earlier age onset of Type 2 diabetes in the US population portends a rise in the clinical diagnosis of DPN. Moreover, the complex etiology of DPN has rendered treating this complication problematic. These facts increase the urgency to more fully understand how hyperglycemia affects the interplay of molecular signals operative in affecting the rate of neuronal degeneration and regeneration in DPN. Although both vascular and metabolic insults contribute to DPN, it is well recognized that an altered neurotrophism contributes to its physiological progression. Our lab focuses on identifying how hyperglycemia may alter specific growth factor signaling pathways in neurons and glia and affect the rate of demyelination and remyelination of peripheral nerves.

The lab currently has two main projects. One project focuses on defining the effect of hyperglycemia and IGF-1 signaling in regulating superoxide generation and alterations of the mitochondrial proteome. This project uses both biochemical assessments of mitochondrial function and state of the art quantitative proteomic analyses to identify how hyperglycemia and growth factor signaling intersect at the level of superoxide generation to affect the mitochondrial proteome and mitochondrial function.

The second project examines the hypothesis that the segmental demyelination in DPN may arise, in part, from an altered neuregulinism. The possible contribution of altered neuregulinism in DPN is examined using cell culture models of myelinated sensory axons and in novel conditional transgenic animal models that we have generated which express constitutively active and dominant-negative forms of various neuregulin receptors. Successful students in the lab will typically have a clear commitment to a career in science, a strong work ethic and develop the ability to integrate biochemical, morphological, pharmacological and molecular biological approaches to answer basic questions in signal transduction. Interested students are welcomed and encouraged to contact me directly regarding our ongoing research activities and the possibility of pursuing undergraduate research, graduate training or serving as a post-doctoral fellow in the lab.

Selected Publications —

Rick Dobrowsky Publications (PubMed)